Production of alpha-L-iduronidase in maize for the potential treatment of a human lysosomal storage disease

Xu He, Thomas Haselhorst, Mark von Itzstein, Daniel Kolarich, Nicolle H. Packer, Tracey M. Gloster, David J. Vocadlo, Lorne A. Clarke, Yi Qian, Allison R. Kermode

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19 Citations (Scopus)


Lysosomal storage diseases are a class of over 70 rare genetic diseases that are amenable to enzyme replacement therapy. Towards developing a plant-based enzyme replacement therapeutic for the lysosomal storage disease mucopolysaccharidosis I, here we expressed alpha-L-iduronidase in the endosperm of maize seeds by a previously uncharacterized mRNA-targeting-based mechanism. Immunolocalization, cellular fractionation and in situ RT-PCR demonstrate that the alpha-L-iduronidase protein and mRNA are targeted to endoplasmic reticulum (ER)-derived protein bodies and to protein body-ER regions, respectively, using regulatory (5'- and 3'-UTR) and signal-peptide coding sequences from the gamma-zein gene. The maize alpha-L-iduronidase exhibits high activity, contains high-mannose N-glycans and is amenable to in vitro phosphorylation. This mRNA-based strategy is of widespread importance as plant N-glycan maturation is controlled and the therapeutic protein is generated in a native form. For our target enzyme, the N-glycan structures are appropriate for downstream processing, a prerequisite for its potential as a therapeutic protein.

Original languageEnglish
Article number1062
Pages (from-to)-
Number of pages9
JournalNature Communications
Publication statusPublished - Sept 2012


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